OR16. HLA epitope-mismatch more precisely predicts the development of de novo donor specific antibody and acute cellular rejection after lung transplant

Abstract

Aim Development of de novo HLA donor-specific antibody (dnDSA) after lung transplant (LuTx) is prevalent and associated with poorer transplant outcomes. Understanding pre-LuTx determinants helps to minimize dnDSA. The aim of this study was to investigate the impact of HLA-Epitope Mismatch Load (EpiMML) in the development of dnDSA in LuTx recipients. Methods 572 recipients received LuTx during 10/2012–10/2017 and were retrospectively analyzed for the formation of dnDSA (Mean Fluorescence Intensity ⩾ 1000). Antigenic mismatches were recorded among 422 recipients. EpiMMLs were determined by HLA-Matchmaker (Version 02) among 168 recipients who had four-digit high resolution typing. There were 18 recipients who were typed by both high and low resolution. Acute Cellular Rejection (ACR) and Antibody Mediated Rejection (AMR) were assessed for LuTx outcomes. Results Of the 572 patients, 55% developed dnDSA; 25% Class I, 39% Class II, and 36% both Class I and II. In Class II, the most prevalent dnDSA was DQ (216/235; 92%). EpiMMLs for Class I, Class II, as well as single loci of HLA-A, B, C, DR, and DQ were all significantly higher from patients with positive dnDSA than from patient with negative dnDSA (Table 1a). However, for antigen-level mismatches, only HLA-A and DQ correlated with the development of dnDSA. As shown in Table 1b, certain mismatched epitopes were more frequent among patients who developed dnDSA than those who did not. Among a subgroup of 120 recipients, EpiMMLs of Class II, especially DQ, were significantly associated with the occurrence of ACR (p = 0.02 and 0.005, respectively). There was no remarkable relevance between EpiMMLs and AMR. Conclusions Compared to HLA antigen mismatching, EpiMML is a better predictor of dnDSA development in LuTx recipients. Increasing EpiMMLs, particularly for HLA-DQ, identify patients at the highest risk to develop dnDSA and ACR. Collectively, these data support the use of EpiMML assessment especially for optimizing post-transplantation immunosuppression in LuTx recipients. Download : Download high-res image (242KB) Download : Download full-size image Download : Download high-res image (182KB) Download : Download full-size image